433694-46-3

ETS variant 1 (ETV1) is a transcription factor oncogene implicated in several cancers where it has been altered by chromosomal translocation, gene amplification, or lineage dysregulation. The ETV1 transcription factor is phosphorylated downstream of MAPK signaling and is acetylated at lysines 33 and 116 by the histone acetyltransferase p300. Both of these events increase the protein half-life of ETV1 and enhance its transcriptional activity. BRD32048 is a substituted [1,3,5]triazine derivative that inhibits ETV1 transcriptional activity by binding to ETV1 (K_D = 17.1 μM in vitro), which reduces p300-dependent acetylation and stability of ETV1 and, thereby, promotes its degradation. At 20-100 μM, BRD32048 can dose-dependently prevent invasion of ETV1-reliant cancer cells in in vitro models.

BRD32048 is a direct binder of ETV1 with a KD of 17.1 μM. BRD32048 modulates both ETV1-mediated transcriptional activity and invasion of ETV1-driven cancer cells. BRD32048 inhibits ETV1 acetylation and promotes its degradation. BRD32048 acts as a top candidate ETV1 perturbagen[1].

ChEBI: N2-(4-methoxyphenyl)-6-(1-piperidinylmethyl)-1,3,5-triazine-2,4-diamine is a member of methoxybenzenes and a substituted aniline.

[1] Marius S Pop, et al. A small molecule that binds and inhibits the ETV1 transcription factor oncoprotein. Mol Cancer Ther. 2014 Jun;13(6):1492-502. DOI:10.1158/1535-7163.MCT-13-0689